The invention generally relates to proteins, particularly elastin-mimetic proteins, and methods of producing and using the same, such as in medical devices and/or medical procedures, and other applications.
Cardiovascular disease is a growing concern whose importance in the health care field is evidenced by the effort directed at tissue engineering of artificial blood vessels. Current procedures for alleviating cardiovascular disease such as coronary artery disease involves use of a variety of stents, bypass vessels and/or angioplasty. A common problem with these techniques is the high rate of restonosis that requires one or more additional procedures to ensure blood flow through the region remains effective. One method to assist in reducing subsequent adverse outcome or failure of the procedure is to ensure any implanted device be mechanically matched to the surrounding vessel. In addition, any implanted material must also be biocompatible to avoid or minimize an unwanted immune response and anti-thrombogenic to minimize unwanted platelet adhesion.
One difficulty with producing biocompatible and mechanically matched devices such as grafts, stents and artificial blood vessels is that the physical characteristics of the blood vessel is rather complex due to the interaction of a number of different biological materials including elastin, collagen and glucoseaminoglycans, for example. Elastin provides initial elasticity to the vessel wall in the lower strain regime, while collagen prevents overextension of the blood vessel. Accordingly, elastin is an important material that provides elasticity to the blood vessel wall and any implantable medical device in the cardiovascular should model elastin's physical characteristics.
Although elastin-mimetic proteins are generally known in the art (see, e.g., U.S. Pub. No. 2004/0171545 published Sep. 2, 2004), there is a need for such proteins having improved mechanical performance that better match the surrounding in vivo environment while being durable and readily and reliably made. In particular, the cardiovascular system has a wide range of operating parameters depending on the location within the vascular tree. For example, the stress exerted on a blood vessel wall in the heart or aorta is very different in terms of magnitude and oscillation than those stresses exerted in the venous system. The venous system tends to be of lower and constant pressure whereas upstream in the arterial system the systolic and diastolic pressures provide continuous and significant cyclic strain on the vessel wall. In addition, the pressure and time-dependent forces exerted in a neurovascular defect (e.g., aneurysm) region may be quite different than that in other blood vessels. These difference in the mechanical environment are optionally addressed herein by artificial elastin-mimetic proteins (and related methods of manufacture) that are readily modified to provide a mechanical parameter that is matched to the in vivo environment.